Methylthioadenosine phosphorylase gene deletions are frequently detected by fluorescence in situ hybridization in conventional chondrosarcomas.

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Chow WA, Bedell V, Gaytan P, Borden E, Goldblum J, Hicks D, Slovak ML

Methylthioadenosine phosphorylase gene deletions are frequently detected by fluorescence in situ hybridization in conventional chondrosarcomas.

Cancer Genet Cytogenet. 2006 Apr 15;166(2):95-100.

PubMed ID

16631464 [ View in PubMed

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Abstract

Chondrosarcomas are the second most common primary malignant tumor of bone. Chemotherapy for conventional chondrosarcomas is generally ineffective. Methylthioadenosine phosphorylase (MTAP) is a ubiquitous enzyme, essential in the salvage pathway of adenine and in methionine synthesis. MTAP-deficient cells are more susceptible than wild-type cells to pharmacologic inhibitors of de novo purine synthesis. Homozygous deletions of MTAP have been reported in hematologic and solid tumor malignancies. Based on these observations, we investigated the frequency of MTAP deletions in conventional, grade II chondrosarcomas by fluorescence in situ hybridization (FISH) analysis: 23 conventional, grade II chondrosarcoma patient samples from the Cleveland Clinic Foundation were analyzed for MTAP deletions. Nuclei were successfully extracted from 14 of 23 samples (61% evaluable) for FISH analysis: 7 of 14 samples (50%) showed either homozygous or hemizygous deletion of the MTAP gene, 6 of 14 (43%) failed to show deletion, and 1 of 14 (7%) was inconclusive. These findings suggest that approximately one-half of conventional, grade II chondrosarcomas may be preferentially sensitive to pharmacologic inhibitors of de novo purine synthesis. The present study led to development by the Intergroup Coalition Against Sarcomas of a phase II trial of pemetrexed, a multitargeted anti-folate, for advanced chondrosarcomas.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Adenine	S-methyl-5'-thioadenosine phosphorylase	Protein	Humans	Unknown	Not Available	Details